Association Between the Intracellular Tacrolimus Concentration in CD3+ T Lymphocytes and CD14+ Monocytes and Acute Kidney Transplant Rejection

Suwasin Udomkarnjananun*, Marith I. Francke, Marjolein Dieterich, Daan van de Velde, Jeroen G.H.P. Verhoeven, Karin Boer, Marian C. Clahsen-Van Groningen, Brenda C.M. De Winter, Carla C. Baan, Dennis A. Hesselink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Background:Intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) (TAC [PBMC]) has been proposed to better represent its active concentration than its whole blood concentration. As tacrolimus acts on T lymphocytes and other white blood cells, including monocytes, we investigated the association of tacrolimus concentration in CD3 +T lymphocytes (TAC [CD3]) and CD14 +monocytes (TAC [CD14]) with acute rejection after kidney transplantation.Methods:From a total of 61 samples in this case-control study, 28 samples were obtained during biopsy-proven acute rejection (rejection group), and 33 samples were obtained in the absence of rejection (control group). PBMCs were collected from both cryopreserved (retrospectively) and freshly obtained (prospectively) samples. CD3 +T lymphocytes and CD14 +monocytes were isolated from PBMCs, and their intracellular tacrolimus concentrations were measured.Results:The correlation between tacrolimus whole-blood and intracellular concentrations was poor. TAC [CD3]was significantly lower than TAC [CD14](median 12.8 versus 81.6 pg/million cells; P < 0.001). No difference in TAC [PBMC](48.5 versus 44.4 pg/million cells; P = 0.82), TAC [CD3](13.4 versus 12.5 pg/million cells; P = 0.28), and TAC [CD14](90.0 versus 72.8 pg/million cells; P = 0.27) was found between the rejection and control groups. However, freshly isolated PBMCs showed significantly higher TAC [PBMC]than PBMCs from cryopreserved samples. Subgroup analysis of intracellular tacrolimus concentrations from freshly isolated cells did not show a difference between rejectors and nonrejectors.Conclusions:Differences in TAC [CD3]and TAC [CD14]between patients with and without rejection could not be demonstrated. However, further optimization of the cell isolation process is required because a difference in TAC [PBMC]between fresh and cryopreserved cells was observed. These results need to be confirmed in a study with a larger number of patients.

Original languageEnglish
Pages (from-to)625-632
Number of pages8
JournalTherapeutic Drug Monitoring
Volume44
Issue number5
DOIs
Publication statusPublished - 1 Oct 2022

Bibliographical note

Funding Information:
S. Udomkarnjananun received a grant from the King Chulalongkorn Memorial Hospital and Thai Red Cross Society for conducting research at the Erasmus MC.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.

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